GASTROINTESTINAL EFFECTS OF OPIOIDS

Opioids decrease gastrointestinal motility,^[259] and this action underlies their use as antidiarrheal agents. Patients receiving parenteral opioid therapy preoperatively are more likely to have "full stomachs" regardless of their "NPO" status.

Several opioid receptor types can be demonstrated on myenteric neurons, and both κ- and μ-receptor agonists regulate cholinergic transmission in the myenteric plexus. κ-Receptor agonists appear to modulate acetylcholine release more potently than μ-receptor agonists by inhibition of N-type voltage-sensitive Ca²⁺ channels via a pertussis toxin-sensitive G protein in guinea pig ileum.^[260]

Opioids alter lower esophageal sphincter activity, resulting in sphincter relaxation.^[261] Gastric emptying is delayed by opioids, via supraspinal (vagus nerve-mediated) and spinal, as well as peripheral, mechanisms. Both fentanyl and meperidine reduce antroduodenal motility during balanced anesthesia, but at least partial recovery occurs relatively early (0.5–2.0 hours) postoperatively.^[262] Both opioids are also associated with an increase in gastric pH. Tramadol (1.25 mg/kg IV) has a measurable but smaller inhibitory effect on gastric emptying compared with codeine (1 mg/kg IV) or morphine (0.125 mg/kg IV).^[263] Opioids administered epidurally as well as intrathecally reduce gastrointestinal motility.^{[264] [265]}

Naloxone reverses opioid-induced delays in gastric emptying. Methylnaltrexone, a quaternary naloxone derivative that dose not cross the blood-brain barrier, can attenuate morphine-induced delays in gastric emptying, suggesting that a peripheral mechanism is involved in the opioid effect on the gastrointestinal tract. ^[259] Intravenous, but not intramuscular, metoclopramide (10 mg) also can reverse morphine-induced delays in gastric emptying.^[266]

Opioid effects on the intestine are complex. Transit time from mouth to ileum may not be significantly altered by morphine, because morphine enhances ileal propulsion before decreasing motility. Opioids increase tone and decrease propulsive activity in most of the intestine. Gastrointestinal secretions can be increased by opioids.

The effects of opioids on intestinal circulation are complex and are not completely understood. Fentanyl increases intestinal blood flow in a dose-dependent fashion.

Biliary and Hepatic Effects

All opioid agonists increase biliary duct pressure and sphincter of Oddi (choledochoduodenal sphincter) tone in a dose- and drug-dependent manner through opioid receptor-mediated mechanisms.^[267] However, the clinical consequences of opioid-induced biliary tract actions are usually minimal. Increases in biliary pressure caused by opioids are, with the exception of meperidine, reversible with naloxone.

Meperidine has a dual effect on the biliary tract.^[268] Low concentrations of meperidine produce an inhibitory effect on the response of the common bile duct to electrical stimulation. Higher concentrations produce an excitatory effect and increase spontaneous contractions. Neither of these responses is affected by naloxone.

Opioids produce mild effects on liver function during anesthesia and surgery. In rats, fentanyl produces a postanesthetic dysfunction of the liver that is independent of the presence of cirrhosis. Alfentanil can reduce hepatic artery blood flow by more than 50% in the dog.^[256]